A Phase 1b, multi-center, randomized, double-blind, vehicle-controlled study was conducted in 48 adult patients with mild-to-moderate atopic dermatitis (AD). 17, and 14 patients received SB414 2% cream, SB414 6% cream and vehicle, respectively, twice daily for 2 weeks. SB414 showed trends suggestive of efficacy based on the change in eczema area severity index (EASI), itch numerical rating score (NRS) and target lesion severity score. Both SB414 2% and 6% were well tolerated, but 2% had a more favorable local tolerability profile with no quantifiable systemic exposure. Skin biopsies were obtained at baseline and Week 2 from a representative target lesion (LS) and from non-lesional skin (NL) at baseline. Gene expression analyses were conducted to assess lesional changes from baseline in the SB414 2%, 6% and vehicle-treated groups and difference between groups, as well as comparing with NL. Quantitative RT-PCR was performed using TaqMan Low Density Array (TLDA). Biomarkers from the Th2 and Th22 inflammatory pathways known to be highly associated with AD, including Interleukin 13 (IL-13), IL-4R, IL-5 and IL-22, were downregulated after two weeks of treatment with SB414 2%, achieving statistically significant 10.5 (p<0.01), 2.5 (p<0.01), 7.1 (p<0.05) and 7.5-fold (p<0.05) reductions over vehicle, respectively. The changes in Th2 and Th22 biomarkers as well as Th17 markers including IL-17A and IL-17F and clinical efficacy assessed as the percent change in EASI scores were significantly correlated in patients treated with SB414 2%. Overall, topical nitric oxide releasing 2% SB414 cream but not vehicle or 6% cream induced significant changes in AD biomarkers after 2 weeks of treatment. Further studies are ongoing.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Conventional post-operative radiotherapy (cPORT), given in 25-30 fractions (2Gy per fraction) over 5-6 weeks, is associated with improved locoregional control but also with skin toxicity, fibrosis, and wound healing issues. We hypothesized that 1-3 fractions of 8Gy hypofractionated PORT (hPORT), may provide adequate control in the majority of patients with significantly diminished toxicity and a less extensive treatment regimen. 17 patients with locoregional MCC were identified from our prospective registry that received hPORT after an informed discussion that included cPORT versus receiving no RT. The in-field recurrence rate (per site treated) was estimated using the Kaplan-Meier method. 12 patients had local and 5 had nodal MCC with a median age of 75 years. Median follow-up was 483 days. Patients received either 8Gy single-fraction RT (n¼15) or 24Gy in 3 daily fractions (n¼2) in the initial (n¼11) or recurrent (n¼6) setting. RT fields (n¼23) encompassed 17 primary tumor beds and 6 regional node beds. The 1-year recurrence rate infield was 5.0% by Kaplan-Meier estimation. During the entire follow-up period, the in-field recurrence rate was 3/23 (13%). Toxicity was limited to localized skin changes (no greater than CTCAE v5 grade 1), typically for 2-3 days. Supporting the concept that hPORT is effective in controlling local MCC, at 6 months after RT, one patient developed two in-transit recurrences outside the hPORT field, but nowhere within the field. These early findings suggest hPORT can be a viable alternative to cPORT with a low rate of in-field recurrence and minimal toxicity that compare favorably with cPORT. We propose further investigation of hPORT, especially in MCC patients with significant co-morbidities and/or high competing risk of distant metastases.

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BackgroundMerkel cell carcinoma (MCC) is twice as likely to recur in immunosuppressed (IS) patients as in immunocompetent (IC) patients. Iatrogenic IS due to autoimmune disease (AD) may influence prognosis differently than intrinsic IS such as due to hematologic malignancy. Moreover, modification of IS medication may improve prognosis.ObjectivesOur objective was to evaluate the risk of MCC recurrence among patients with AD diseases relative to other immunosuppressive conditions among 762 MCC patients from an Institutional review board-approved registry.MethodsWe categorized patients into 3 groups: IS due to AD (ISAD); IS from other causes (lSnon-AD) such as hematologic malignancy, solid organ transplant, human immunodeficiency virus; or immune competent (n=31, 70, and 661 respectively). ISAD patients were subcategorized into rheumatoid arthritis (RA) (ADRA, n=13) vs. AD except for RA (ADnon-RA, n=18). Descriptive statistics were used to compare the features of different characteristics in each group. Kaplan-Meier survival curves were constructed to assess the cumulative incidence of recurrence in different patient groups. In order to estimate the associations between baseline patient characteristics and the risk of MCC recurrence, Fine and Gray regression models were used with death as a competing risk for recurrence. The multivariable models adjusted for age, sex, and extent of MCC at initial presentation.ResultsPatients with ISAD had lower stage disease (local disease: 58% vs. 36%, p = 0.003) and smaller primary tumors than ISnon-AD (<= 2 cm: 83% vs. 57%, p=0.023). After adjusting for age, sex, and stage, ISAD patients (ADRA and ADnon-RA) overall had a 54% higher recurrence rate (hazard ratio (HR): 1.54, p=0.21) than IC patients. In comparison, ISnon-AD group had a 165% higher recurrence rate (HR: 2.65, p<0.001) than IC patients (Figure 1). When considered separately, ADRA pts appeared to have a similar recurrence rate as IC pts (HR: 1.19, p=0.76) while ADnon-RA pts had a higher recurrence rate (HR: 1.83, p=0.16) relative to IC pts. At the time of MCC diagnosis, 80% (n=24) of AD pts were on IS medication including conventional disease modifying drugs, biologics, or oral steroids. After MCC diagnosis, 22% (5 patients) stopped all immunosuppressive medications. Among patients on biologics, 89% (8/9 pts) elected to stop the drug. Eleven pts with AD experienced recurrences. Our study was underpowered to demonstrate associations regarding use of a particular immunosuppressive medication and MCC recurrence.Figure 1.Cumulative incidence of Merkel cell carcinoma recurrence in different patient groups.AD = autoimmune disease; IS = immunosuppressed; RA = rheumatoid arthritis.There were 4/13, 8/18, 49/70, and 217/661 recurrences in the RA, ADnon-RA, other immunosuppressed, and not chronically immunosuppressed groups, respectively. Follow-up time ranged from 26 days to 16 years, with median follow-up times of 4.7 years, 1.6 years, 1.6 years, and 3.9 years for the RA, ADnon-RA, other immunosuppressed and not chronically immunosuppressed groups, respectively.ConclusionIn this cohort, pts with AD appeared to have a better prognosis than intrinsic IS, with RA conferring very little risk above that for immune competent pts.AcknowledgementsI have no acknowledgements to declare.Disclosure of InterestsNone declared